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Identification of Novel Proteinase K-resistant C-terminal Fragments of PrP in Creutzfeldt-Jakob Disease.
- Source :
-
Journal of Biological Chemistry . 10/17/2003, Vol. 278 Issue 42, p40429-40436. 8p. 1 Diagram, 2 Charts, 12 Graphs. - Publication Year :
- 2003
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Abstract
- The central event in the pathogenesis of prion diseases, a group of fatal, transmissible neurodegenerative disorders including Creutzfeldt-Jakob disease (CJD) in humans, is the conversion of the normal or cellular prion protein (PrP[sup C]) into the abnormal or scrapie isoform (PrP[sup Sc]). The basis of the PrP[sup C] to PrP[sup Sc] conversion is thought to involve the diminution of α-helical domains accompanied by the increase of β structures within the PrP molecule. Consequently, treatment of PrP[sup Sc] with proteinase K (PK) generates a large PK-resistant C-terminal core fragment termed PrP27-30 that in human prion diseases has a gel mobility of ∼19-21 kDa for the unglycosylated form, and a ragged N terminus between residues 78 and 103. PrP27-30 is considered the pathogenic and infectious core of PrP[sup Sc]. Here we report the identification of two novel PK-resistant, but much smaller C-terminal fragments of PrP (PrP-CTF 12/13) in brains of subjects with sporadic CJD. PrP-CTF 12/13, like PrP27-30, derive from both glycosylated as well as unglycosylated forms. The unglycosylated PrPCTF 12/13 migrate at 12 and 13 kDa and have the N terminus at residues 162/167 and 154/156, respectively. Therefore, PrP-CTF12/13 are 64-76 amino acids N-terminally shorter than PrP27-30 and are about half of the size of PrP27-30. PrP-CTF12/13 are likely to originate from a subpopulation of PrP[sup Sc] distinct from that which generates PrP27-30. The finding of PrP-CTF12/13 in CJD brains widens the heterogeneity of the PK-resistant PrP fragments associated with prion diseases and may provide useful insights toward the understanding of the PrP[sup Sc] structure and its formation. [ABSTRACT FROM AUTHOR]
- Subjects :
- *PROTEINASES
*POTASSIUM
*CREUTZFELDT-Jakob disease
Subjects
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 278
- Issue :
- 42
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 11358013
- Full Text :
- https://doi.org/10.1074/jbc.M308550200